Nerve growth factor (NGF) is a chemically well-defined peptide important to the development and growth of the vertebrate nervous system. For a recent review of the chemistry, biology, and medical implications of NGF please see Mobley et al., New Eng. J. Med. 297:1096, 1149 & 1211 (1977). Certain neuronal tumors, such as neuroblastoma, will respond in culture to NGF by acquiring a more advanced morphology, by biochemical specialization, and by slowing of growth. Thus, the uncontrolled growth and primitive morphology of neuronal tumors may be subject to manipulation, but a fuller understanding of the molecular processes leading to differentiation will be required. The aim of this project is to define the sequence of events beginning with the interaction of NGF with its receptor and which ultimately culminates in neurite outgrowth and increased activity of neuron-specific enzymes in cultured rat pheochromocytoma cells. it is proposed to study the properties of the NGF receptor, to identify and isolate macromolecular elements crucial for neurite outgrowth, and to identify transcriptional, translational, and post-translational regulatory events. Attempts will be made to identify specific and reversible agonists and inhibitors of neurite outgrowth. The majority of studies will be conducted in rat pheochromocytoma cells, but human and mouse neuroblastoma cells and embryonic chick sensory and sympathetic ganglia will also be utilized when advantageous.